NEUROPATHOLOGY CORE (CORE D) - PROJECT SUMMARY/ABSTRACT The Neuropathology Core (NPC) is an essential part of the Alzheimer's Disease Core Center (ADCC). During life, the signs and symptoms of Alzheimer's disease (AD) are not sufficiently different from several other conditions, resulting in misdiagnosis, even at the most advanced centers, in about 20-30% of subjects. Examination of the brain after death by a certified Neuropathologist is therefore the only means by which a definite diagnosis can be attained, allowing all research results to be correctly interpreted. A second major role of the NPC is to provide neuropathologically characterized brain tissue to basic scientists, both within the ADCC and outside it, enabling them to discover the underlying molecular mechanisms of disease and design appropriate therapeutic interventions. A detailed understanding of the genetic and molecular processes of disease pathogenesis, obtained by comparative study of diseased and non-diseased brain tissue, remains the major approach to finding such interventions. A third important goal of the NPC is to help develop a collaborative synergy that will enhance the research productivity of the entire Center. Our Specific Aims are as follows: 1) To provide precise neuropathologic diagnoses of patients that have been clinically studied by the Clinical Core. 2) To provide basic scientists with neuropathologically characterized brain tissue suitable for the elucidation of the molecular mechanisms of AD and related disorders, and especially to assist researchers in their studies of the earliest stages of Alzheimer's disease, with the goal of identifying therapeutic strategies that will prevent the disease or slow its progress. 3) To share neuropathological skills, expertise, knowledge and data with all ADCC investigators and the scientific community at large, facilitating a collaborative synergy that will enhance the research productivity of all.